2-(1-Piperidyl)ethoxyamine dihydrochloride → 4-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(1-piperidyl)ethoxyimino)quinazoline

HRID 220112Notes

Reaction equation

HRID 220112 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25](C=O)[CH:26]=3)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.Cl.Cl.[N:32]1([CH2:38][CH2:39][O:40][NH2:41])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1>O1CCCC1.O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[CH2:26][C:25](=[N:41][O:40][CH2:39][CH2:38][N:32]4[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]4)[CH:24]=[CH:23][C:22]=3[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

6

Reactant 2

HCID 212756742-(1-Piperidyl)ethoxyamine dihydrochlorideHCID 577336564-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino) 6-formylquinazoline

Product 1

HCID 866309154-(3-Chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(1-piperidyl)ethoxyimino)quinazolineYield 20.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

In a mixture of tetrahydrofuran (2 ml) and water (0.1 ml) were dissolved 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-formylquinazoline (IV-1, 50 mg) and 2-(1-piperidyl)ethoxyamine dihydrochloride (36.5 mg), and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed sequentially with aqueous saturated sodium bicarbonate solution, and aqueous sodium chloride solution, and dried over magnesium sulfate. After concentration, the residue was purified by chromatography (eluting with hexane:ethyl acetate=2:3) using an amino column, and further re-purified by thin layer chromatography to obtain 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(2-(1-piperidyl)ethoxyimino)quinazoline (V-1, 13 mg).

Workup

  1. washwashed sequentially with aqueous saturated sodium bicarbonate solution, and aqueous sodium chloride solution
  2. dry with materialdried over magnesium sulfate
  3. concentrationAfter concentration
  4. customthe residue was purified by chromatography (eluting with hexane:ethyl acetate=2:3)
  5. customfurther re-purified by thin layer chromatography

Sources & evidence

ORD record
ord-48c75bf2b9d8478e9c8c418bf796efd7
Source dataset
uspto-grants-2012_06
Patent number
US08202879B2

Reaction notes

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